Loss of bone mass and bone quality is a serious health problem that can be more so in patients of advanced age. After intervention in odontology treatments there is often a loss of bone mass that results in complications and pathologies. This occurs, for example, in alveolar resorption following dental extraction and in periodontal disease. On the other hand, in traumatology and in other surgical interventions, loss of bone mass is a serious health problem that can even result in death of the patient.
For almost a century biomaterials have been used to repair or replace bone segments of the muscular-skeletal system. Autologous bone grafts, that is from the patient himself, are commonly used to fill bone cavities and in surgical reconstructions. However, there is a limited source of bone and these procedures subject patients to additional trauma to obtain the graft. Another option is that of donor allografts. However, these have a slower bone resorption and neoformation, reduced vascularisation and osteogenic capacity, and a greater immune response and risk of transmission of pathogens. An alternative are materials made from bovine bone, such as BioOss®, GenOx Inorg® and Orthoss®, which are commonly used in dentistry. However, the use of these products based on biological materials has problems of possible contamination with infectious agents and requires strict quality controls. With the aim of avoiding these problems synthetic matrices have been developed. Research into new synthetic biomaterials for bone repair has aimed at reducing to a minimum the requirement for bone grafts by means of an artificial equivalent that is reabsorbed in time and/or integrates adjacent bone, and also serves as a support for osteoporotic fractures. The mechanical properties of this artificial bone material should be as close to spongy bone as possible. The material must also contribute to the stability of the fracture and be sufficiently resistant to reduce the time in which immobilisation or external support is required. The replacement material must be biodegradable, biocompatible and osteoinductive, that is it should attract mesenchymal cells close to the implant and favour their differentiation into osteoblasts, and should also be osteoconductive, that is act as a guide for the formation of new bone.
Calcium phosphates have a special interest in bone regeneration because they resemble the mineral phase of natural bone and they are susceptible of bone remodelling and resorption. The most frequently used calcium phosphates include matrices of hydroxyapatite, tricalcium phosphate and brushite. These materials can be administered in the form of cementing pastes, implantable solids or granular or powder formulations.
In the development of bone regeneration matrices a special mention should be given to products which claim improved bone regeneration by means of incorporating a certain degree of porosity. The introduction of porosity in the system considerably increases the surface area of the material at the site of implant and the surface which is susceptible of interacting with cells of the surrounding tissues. Examples of porous hydroxyapatite of coral origin include Interpore® and ProOsteon®. Furthermore, examples of synthetic hydroxyapatite include Apafill-G® or ENGIpore®. Other commercial granular synthetic matrices of beta tricalcium phosphate include chronOs® and Cerasorb®. The latter is commercialised as particles with different sizes between 150 μm and 2000 μm depending on the need, and commonly used in alveolar regeneration after mixing with the patient's blood. Another similar product is Bi-Ostetic™, which is formed by particles between 1000 μm and 2000 μm composed by a mixture of hydroxyapatite and tricalcium phosphate. Furthermore, Collagraft® is another granular material based on hydroxyapatite and tricalcium phosphate which also incorporates collagen. Other synthetic osteoinductive materials incorporated in commercial products such as CalMatrix™ include calcium sulphate.
In the area of materials with growing interest in bone regeneration is dicalcium phosphate dihydrate [CaHPO4.2H2O], of mineralogic name “brushite”, that can be found in nature or synthetically produced by means of acid-base reactions of calcium phosphates (LeGeros et al. 1982 J. Dental Res. 61:343; Brown W E y Chow L C. 1983 J. Dental Res. 62: 672). In the area of the use of brushite, there have been recent descriptions of combinations of brushite and tricalcium phosphate resulting from a manufacturing process with excess tricalcium phosphate. It has been shown that a granular material composed of 87% in mass of brushite and 17% in mass of beta-tricalcium phosphate is more degradable and results in greater bone formation than the commercial bovine hydroxyapatite BioOss® (Tamimi F. et al. 2006 J. Clin. Periodontol 33:922-928).
Dicalcium phosphate [CaHPO4], of mineralogic name “monetite”, is a material considerably different from brushite which can be found as a mineral in nature, synthesised directly, or by a decomposition reaction of brushite. There are a few precedents in the use of monetite in bone regeneration, such as descriptions of the use of natural monetite mineral mixed with blood of the patient (Getter L, et al. 1972 J. Oral Surg. 30:263-268) or its incorporation into protein solutions (WO98/58602) or biodegradable polymers (US2005209704). More recently monetite has been evaluated in animal models of bone regeneration (Tamimi F. et al. 2008 J. Biomed. Mater. Res. 87A:980-988). However, the use of monetite in bone regeneration has not been exploited as it has been considered a material which is not optimum for bone regeneration because of its rapid dissolution and low mechanical strength. An example of this can be found in the formulation of brushite granules (Tamimi F. et al. 2007 J. Biomed. Mater. Res. 81A:93-102) were high temperatures that result in the conversion of brushite into monetite are intentionally avoided.